Date: 2016-12-03
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Society of Hematology (ASH) Annual Meeting
Company: Affimed (Germany)
Product: AFM13
Action
mechanism: bispecific antibody/fusion protein. AFM13 is a first-in-class bispecific NK-cell TandAb®, which binds NK-cells (Natural Killer cells) specifically via CD16A and has a second binding domain for CD30, a cancer specific target. CD16A is expressed on NK-cells, highly potent cytotoxic effector cells of the innate immune system, enabling AFM13 to selectively bind these effector cells. AFM13 redirects the NK-cells to CD30-expressing cancer cells and binds both targets with high affinity, establishing a bridge whereby the NK-cells are activated and redirected to kill the cancer cells. AFM13 is designed to treat CD30-positive malignancies including Hodgkin lymphoma (HL) and T-cell lymphoma (TCL). It is currently being tested in Hodgkin lymphoma patients as a monotherapy (Phase 2) and in combination with Merck's Keytruda® (Phase 1b).
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 3, 2016, Affimed and its collaboration partner, the German Cancer Research Center (DKFZ), Heidelberg, presented a poster (Abstract #1764) sharing additional insights into the mechanism of action of AFM13, a CD30/CD16A-specific NK-cell engager at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition 2016 in San Diego, California. Expanding on previous studies demonstrating synergistic efficacy of AFM13 when combined with checkpoint modulation (e.g. anti-PD-1), the poster identifies other potential future candidates for AFM13 combination therapies, as well as biomarkers that may be predictive of NK-cell responses to AFM13 treatment. In vitro, NK-cell cytotoxicity towards CD30+ tumor cells and IFN-y production were substantially increased in the presence of AFM13, and AFM13 was significantly more potent than a native anti-CD30 IgG1 antibody. A detailed analysis showed that interaction of NK-cells with AFM13-coated tumor cells up-regulated the expression of NK-cell surface receptors such as CD25, CD69 and CD137/4-1BB, as well as additional markers that may serve as NK-cell checkpoints. Importantly, AFM13-mediated CD16A engagement enhanced the potential of NK-cells for proliferation and expansion when subsequently incubated with the cytokines IL-15 or IL-2. This effect was observed even in target cells resistant to naïve NK-cells and to NK-cells activated only with IL-2/IL-15. In summary, the data presented at ASH demonstrates that AFM13 specifically enhances the cytotoxic, proliferative and cytokine-producing potential of NK-cells. In addition, the results indicate that the distinctive modulation of NK-cell receptors can be utilized to monitor NK-cell responses during AFM13 therapy and to select candidates for therapeutic combination strategies. * On October 4, 2016, Affimed announced the presentation of preclinical data on its lead candidate AFM13 at the 16th Annual Meeting of the Society for Natural Immunity in Taormina, Italy. The data, generated in Affimed's collaboration with the Innate Immunity Group of Dr. Adelheid Cerwenka at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, were presented in a poster titled "The bispecific CD30/CD16A TandAb AFM13 amplifies the cytolytic and proliferative potential of NK-cells" yesterday, October 3, 2016. In this preclinical study, the specific phenotype and functionality of human NK-cells when redirected to AFM13-coated tumor cells, as well as their responsiveness to cytokines, were analyzed. The results show that AFM13 improves NK-cell cytotoxicity against CD30+ tumor cells that are resistant to naïve NK-cells. Using CFSE-labelled NK-cells, the researchers demonstrated that AFM13 amplifies cytokine-mediated NK-cell proliferation and expansion by enhancing the NK-cells' sensitivity to IL-2 and IL-15. These data indicate that cytokine administration in combination with AFM13 might potentially enhance NK-cell activity in the tumor microenvironment.
